title: Optimized strategies to synthesize β-cyclodextrin-oxime conjugates as a new generation of organophosphate scavengers.
abstract: A new generation of organophosphate (OP) scavengers was obtained by synthesis of β-cyclodextrin-oxime derivatives 8-12. Selective monosubstitution of β-cyclodextrin was the main difficulty in order to access these compounds, because reaction onto the oligosaccharide was closely related to the nature of the incoming group. For this purpose, non-conventional activation conditions were also evaluated. Intermediates 5 and 7 were then obtained with the better yields under ultrasounds irradiation. Finally, the desired compounds 8-10 were obtained from 5-7 in high purity by desilylation using potassium fluoride. Quaternarisation of compounds 8 and 9 was carried out. OP hydrolytic activity of compounds 8-12 was evaluated against cyclosarin (GF) and VX. None of the tested compounds was active against VX, but these five cyclodextrin derivatives detoxified GF, and the most active scavengers 10 and 11 allowed an almost complete hydrolysis of GF within 10 min. Even more fascinating is the fact that compounds 9 and 10 were able to hydrolyze enantioselectively GF.
authors.affiliation: UMR 6014 & FR 3038 CNRS, rue Tesnière, 76821, Mont-Saint-Aignan Cedex, France.
authors.forename: Romain
authors.initials: R
authors.lastname: Le Provost
authors.forename: Timo
authors.initials: T
authors.lastname: Wille
authors.forename: Ludivine
authors.initials: L
authors.lastname: Louise
authors.forename: Nicolas
authors.initials: N
authors.lastname: Masurier
authors.forename: Susanne
authors.initials: S
authors.lastname: Müller
authors.forename: Georg
authors.initials: G
authors.lastname: Reiter
authors.forename: Pierre-Yves
authors.initials: PY
authors.lastname: Renard
authors.forename: Olivier
authors.initials: O
authors.lastname: Lafont
authors.forename: Franz
authors.initials: F
authors.lastname: Worek
authors.forename: François
authors.initials: F
authors.lastname: Estour
mesh_terms: D006868:Hydrolysis; D007700:Kinetics; D015394:Molecular Structure; D009943:Organophosphorus Compounds / Q000737:chemistry*; D010091:Oximes / Q000138:chemical synthesis*; D013237:Stereoisomerism; D047392:beta-Cyclodextrins / Q000737:chemistry*
chemical_list: D009943:Organophosphorus Compounds; D010091:Oximes; D047392:beta-Cyclodextrins